JP5660533B2 - Current detector - Google Patents

Description

  The present invention relates to an electric current detection apparatus used for electrochemical analysis, biosensor, and chemical sensor. In particular, the present invention relates to a current detection apparatus suitable for measurement of physiologically active substances in body fluids, clinical tests, manufacturing process management of foods, etc., environmental measurement in water, CMOS integrated circuits, and sensor circuits for performing electrochemical measurements.

  Conventionally, there is electrochemical measurement as a method for detecting and quantifying atoms, molecules, and ions dissolved in a solution, and there are methods such as current detection, potential detection, and impedance measurement. Among them, a method for detecting an electric current accompanying an electrochemical reaction is widely used and used for analytical chemistry, biosensors, and chemical sensors. It is applied to physiologically active substances in body fluids, clinical tests, detection of heavy metal ions in waste fluids and foods, production process management of body fluids and foods, and measurement of the environment in water.

  In the current detection type electrochemical measurement, three types of electrodes are used: a working electrode that causes an oxidation-reduction reaction of a substance to be measured, a reference electrode that serves as a reference for potential, and a counter electrode that serves as a dumping place for current flowing from the working electrode. Since the reference electrode serves as a potential reference, no current is allowed to flow. The current generated at the working electrode is processed by the counter electrode, but the potential of the counter electrode and the reaction occurring on the counter electrode are not a problem.

  A device that realizes the operation of such three electrode systems is called a potentiostat. A voltage is applied between the working electrode immersed in the aqueous solution to be measured and the reference electrode, and this voltage application causes an oxidation-reduction reaction of the analyte on the working electrode, and the current value that flows with this reaction is measured. To do the analysis.

  Typical methods for measuring current include amperometry, voltammetry, stripping voltammetry (stripping method), pulse voltammetry, and the like.

  In amperometry, the potential of the working electrode is held in a range where the oxidation-reduction reaction of the substance to be measured occurs with reference to the potential of the reference electrode, and the time change of the current is measured. In a macro electrode having a characteristic length of several mm or more, the amount of current decreases with time. This is because a planar diffusion layer is formed.

  Voltammetry is a method in which the potential applied to the working electrode immersed in the electrolyte solution to be measured is changed and swept while the current at this time is measured based on the potential of the reference electrode. In this method, the concentration of the substance to be measured can be determined from the measured current value. Furthermore, since the type of the substance is known from the potential at which the current starts flowing when the potential is swept, quantitative analysis and qualitative analysis can be performed simultaneously.

  However, in this method, since the sweep is performed by changing the potential, the charging current flowing in proportion to the potential sweep rate, the electrochemical reaction of coexisting species (dissolved oxygen, hydrogen ions, etc.) other than the substance to be analyzed, There is a drawback that a change in the oxidation state of the electrode surface itself is generated as noise.

  An electrode having a characteristic length of several tens of μm or less is called a microelectrode. Microelectrodes have been extensively studied for analyzing microregions in living bodies and small amounts of solution samples, and applications such as measurement of trace substances in sensors and living cells have been attempted.

  Most of the microelectrodes are used by enclosing a metal wire such as platinum or gold, carbon fiber or the like in a glass thin tube. The response behavior of this microelectrode depends on the electrode shape, and as the electrode size decreases, the response speed and S / N ratio improve. In principle, high sensitivity can be achieved, so various electrode shapes and miniaturization have been studied. ing.

  However, when the electrode is miniaturized to the order of μm, the current value that can be detected is reduced to the order of nA or less, and measurement becomes difficult because it becomes sensitive to external noise during measurement. For this reason, it is proposed to increase the absolute current value while maintaining the characteristics such as the high current density of the microelectrodes and the high S / N ratio with respect to the charging current by increasing the number of microelectrodes (arrayed). Yes.

A method of manufacturing a microelectrode array by alternately laminating insulators and conductors has been reported (see, for example, Patent Document 1 and Patent Document 3).
In addition, in the amperometry of microelectrodes, a steady current can be obtained even in a static solution. The substance to be measured can be quantified from this steady current. The reason why the steady current is obtained is that a spherical diffusion layer is formed in the microelectrode, and the expansion of the diffusion layer stops at a certain point and a steady state is obtained.

  By applying different potentials to two adjacent working electrodes in the electrolyte solution, a redox cycle of the redox species occurs, and the current flowing through the working electrode can be amplified (see, for example, Non-Patent Document 1).

  In addition, if a comb electrode that meshes with the two working electrodes is used, it is possible to perform measurement while sweeping one of the comb electrodes and holding the other electrode potential, and thus measurement with little influence of charging current is possible. It is also known that It is known that the lower detection limit in quantitative analysis of metal complexes and the like is improved by using interdigitated comb electrodes (see, for example, Non-Patent Document 2).

  The redox cycle is a phenomenon that occurs when two adjacent electrodes are set to different potentials. When a conductor (macro electrode) with a large area is arranged in the vicinity of a microelectrode to be controlled for potential, one electrode is used. The redox cycle can be caused only by controlling the electric potential of this, which is called a self-induced redox cycle (see, for example, Patent Document 4).

  In the stripping method, a potential at which a substance to be measured is deposited on an electrode is applied, the component is electrolyzed and concentrated on the electrode, and then the current is measured by changing to a potential at which the target component is dissolved. A self-induced redox cycle and a stripping method are combined to determine a concentration of a reversible redox substance (see, for example, Patent Document 2).

Attempts have been made to visualize the concentration distribution of a substance to be measured by performing current detection on each of the microelectrodes arranged in an array (see, for example, Non-Patent Document 4).
For this purpose, there is a technique using a CMOS integrated circuit. It has been reported that a circuit for performing electrochemical measurement such as a potentiostat is incorporated on a semiconductor chip to perform multi-channel electrochemical measurement. If the system includes only the reference electrode and the counter electrode, it can be realized by using one operational amplifier. By connecting the reference electrode to the inverting input terminal of the operational amplifier and the counter electrode to the output terminal, feedback is applied through the solution, and the potential of the reference electrode is held at the potential applied to the non-inverting input terminal from the virtual short circuit.

Furthermore, it has been reported that an electrode is formed on a chip by combining a standard CMOS process with a post process for forming an electrode, and an electrochemical measurement is performed on the chip.
In addition, a method has been reported in which cells having switches attached to electrodes are arranged in an array as a working electrode to obtain a two-dimensional current distribution (see, for example, Non-Patent Document 3).

The characteristics necessary for a circuit for performing a current detection type electrochemical measurement include two points: that the current can be measured while holding the potential of the electrode, and that the input impedance is low.
There is an existing current detection circuit using an operational amplifier and a resistor. This circuit holds an electrode potential by a virtual short circuit of an operational amplifier, and detects current by converting current into voltage through a resistor. It is conceivable to increase the dynamic range by periodically discharging a capacitor instead of a resistor.

JP 2006-78404 A JP-A-6-27081 JP-A-5-281181 JP-A-3-238350

J. et al. Electroanal. Chem. , Preliminary notes, 267, pp. 291 1989 Anal. Chem. , 62, pp. 447, 1990 Sensors and Actuators A.S. , 135, pp. 315, 2007 Biosensors & Bioelectronics. , 15 pp. 523-529 2000

  However, in the current detection method using the microelectrode, it takes several seconds to several tens of seconds until a steady current is observed. For this reason, after waiting for a steady current to be observed in a plurality of electrodes, it takes a very long time to measure one by one in order. Therefore, in order to detect the currents of a plurality of electrodes at high speed, it is necessary to hold the potentials of all the electrodes, keep a steady current flowing through all the electrodes, and sequentially read them. However, a circuit in which a plurality of electrodes are connected to one current detection circuit via a switch cannot hold the potential of an electrode that is not connected to the current detection circuit. For this reason, there is a problem that it is difficult to keep the potentials of a plurality of electrodes at the same time and keep a steady current from flowing, and to perform high-speed measurement.

Furthermore, if current detection is simultaneously performed on microelectrodes integrated at high density, the diffusion layers of the electrodes overlap. As a result, reactants are held between adjacent electrodes, and local measurement becomes difficult. Then, a planar diffusion layer is formed over the plurality of current detection cells (S _{11 to} S ₃₃ ) in the same manner as the flat electrode, and linear diffusion is performed. As a result, the amount of current decreases with time, and no steady current is observed. Thereby, there exists a problem that fixed_quantity | quantitative_assay of a reactant becomes difficult.

  The present invention has been made in view of such problems, and even when current detection is simultaneously performed on highly integrated microelectrodes, the diffusion layers of the electrodes do not overlap and current that enables high-speed and accurate current detection is achieved. An object is to provide a detection device.

The invention according to claim 1, which has been made to solve such a problem, is provided in a plurality on a semiconductor substrate and surrounds the periphery of the working electrode (W _{11 to} W ₃₃ ) and the working electrode (W _{11 to} W ₃₃ ). , Current detection cells (S _{11 to} S ₃₃ ) having auxiliary electrodes (a _{11 to} a ₃₃ ) held at a predetermined potential so that a redox reaction opposite to that of the working electrodes (W _{11 to} W ₃₃ ) occurs. When connected to the working electrode _(W 11 _{~W 33),} it detects a current outputted from the working electrode _(W 11 _{~W 33),} as a working electrode _(W 11 _{~W 33)} becomes a predetermined potential a control current-detecting means (80), is connected to the working electrode _(W 11 _{to W-33),} the potential holding means for holding a working electrode _(W 11 _{to W-33)} to a predetermined potential and (86), current detecting means (80) and a plurality of current detection cells A first switch (Sa _{11 to} Sa ₃₃ ) connected between the working electrodes (W _{11 to} W ₃₃ ) of (S _{11 to} S ₃₃ ), a potential holding means (86), and a plurality of current detection cells ( Any of the second switches (Sb _{11 to} Sb ₃₃ ) connected between the working electrodes (W _{11 to} W ₃₃ ) of S _{11 to} S ₃₃ , and the first switches (Sa _{11 to} Sa ₃₃ ) or one was turned on, while turning off the other first switch to the oN _(Sa 11 _{-SA 33),} among the second switch _(Sb 11 _{~Sb 33),} a first switch (Sa you check _{11 to} Sa ₃₃ ), the second switches (Sb _{11 to} Sb ₃₃ ) connected to the working electrodes (W _{11 to} W ₃₃ ) connected to the other switches (Sb _{11 to} Sb ₃₃ ) are turned off, and the other second switches (Sb _{11 to} Sb _33). ) The switching operation, all the first switch _(Sa 11 _{-SA 33)} and a second switch _(Sb 11 _{to SB 33)} sequentially executes control means and (74), current and further comprising a detection for Device (70).

According to the current detecting device (70), while maintaining the state always current flows held to a predetermined potential the potential of the working electrode (W ₁₁ to _W-33), a plurality of working electrodes (W ₁₁ to W- ₃₃ ) Since the currents are detected by sequentially switching, the potentials of a plurality of electrodes can be held simultaneously, and a steady current can be kept flowing, so that high-speed current detection becomes possible.

Surrounds the periphery of the auxiliary electrode of the working electrode _{(W 11 ~W 33) (a} 11 ~a 33), the working electrode (W ₁₁ ~W ₃₃₎ and the auxiliary electrode as the opposite redox reaction occurs (a ₁₁ ~ Since the potential of a ₃₃ ) is maintained at a predetermined potential, the diffusion layers of the electrodes do not overlap even when current detection is simultaneously performed on the microelectrodes integrated with high density.

Therefore, reactants are not exchanged between adjacent electrodes, and local current detection is possible. Then, in the whole of the plurality of current detection cells (S _{11 to} S ₃₃ ), a planar diffusion layer is not formed as in the case of the flat electrode, and linear diffusion is not performed. As a result, since the amount of current does not decrease with time, a steady current can be observed. This allows accurate quantification of the reactants.
The current detection device (70) according to claim 2 is the current detection device (70) according to claim 1, wherein the current detection means (80) includes an inverting terminal (81) and a non-inverting input terminal (83). an amplifier (82) having the inverting terminal (81) via a first switch (Sa ₁₁ -SA _33), is connected to the working electrode (W ₁₁ to _W-33), the non-inverting terminal (83) , characterized in that it is connected to the working electrode through a second switch _{(Sb 11 ~Sb 33) (W} 11 ~W 33).
According to such a current detection device (70), the current detection device (70) can be easily configured using the amplifier (82) having the inverting terminal (81) and the non-inverting terminal (83).

Current detecting apparatus according to claim 3 (70), in the current detector according to claim 1 or claim 2 (70), an input terminal connected to the working electrode (W ₁₁ to _W-33), the It has an output terminal connected to the first switch (Sa ₁₁ ~Sa ₃₃₎ and a second switch (Sb ₁₁ ~Sb _33), the output current of the working electrode that is input to the input terminal (W ₁₁ ~W ₃₃₎ A current buffer circuit (b _{11 to} b ₃₃ ) in the current detection cell (S _{11 to} S ₃₃ ) that holds the potential of the working electrode (W _{11 to} W ₃₃ ) at a predetermined potential. Features.

According to the current detecting device (70), for outputting to duplicate the current of the working electrode current buffer circuit (b ₁₁ ~b ₃₃₎ is connected to the input terminal (W ₁₁ to _W-33), the switch Variation in electrode potential due to switching can be suppressed.

Current detecting device according to claim 4 (70), in the current detecting apparatus according to claim 3 (70), a current buffer circuit (b ₁₁ ~b ₃₃₎ is the working electrode (W ₁₁ to _W-33) A current mirror circuit for replicating the current and a source follower circuit for holding the current of the working electrodes (W _{11 to} W ₃₃ ) at a predetermined potential are provided.

According to the current detecting device (70), a large power consumption in the current sensing cell, without using a large op occupied area, because it can realize the current buffer circuit (b ₁₁ ~b _33), power consumption And the occupation area can be reduced.

Current detecting device according to claim 5 (70), in the current detecting device according to any one of claims 1 to 4 (70), the width of the auxiliary electrode (a ₁₁ ~a ₃₃₎ is acting It is characterized by being 1/2 or more of the width of the electrodes (W _{11 to} W ₃₃ ).

According to the current detecting device (70), it is possible to sufficiently handle the product produced at the working electrode (W ₁₁ to _W-33) with the auxiliary electrode (a ₁₁ ~a _33), the diffusion layer is the working electrode (W _{11 to} W ₃₃ ), and the diffusion layers of the electrodes do not overlap. Therefore, the quantitative determination of the reactant can be made more accurate.

Current detecting device according to claim 6 (70), in the current detecting device according to any one of claims 1 to 5 (70), the working electrode (W ₁₁ to _W-33) and the auxiliary electrode ( spacing a ₁₁ ~a ₃₃₎ is characterized by less than the diffusion length of the analyte.

If the distance between the working electrode (W _{11 to} W ₃₃ ) and the auxiliary electrode (a _{11 to} a ₃₃ ) is sufficiently smaller than the diffusion distance of the substance to be measured, the redox cycle occurs efficiently, so the working electrode (W _{11 to} W _{33 33} ) current is amplified. Therefore, since it is not influenced by noise, the quantification of the reactant can be made more accurate.

Current detecting device according to claim 7 (70), in the current detecting device according to any one of claims 1 to 6 (70), the working electrode (W ₁₁ to _W-33) and the auxiliary electrode ( a _{11 to} a ₃₃ ) are characterized in that there is no material having a height greater than the diffusion distance of the substance to be measured from the electrode surface.

If there is a step of diffusion distance over the height of the analyte from the electrode surface during the working electrode (W ₁₁ ~W ₃₃₎ and the auxiliary electrode (a ₁₁ ~a _33), the working electrode (W ₁₁ to W- because the products produced in ₃₃₎ can be sufficiently processed by the auxiliary electrode (a ₁₁ ~a _33), the diffusion layer is the working electrode (W ₁₁ to _W-33) remains in the vicinity of, not overlapping the diffusion layer of each electrode. Therefore, the quantitative determination of the reactant can be made more accurate.

It is a lineblock diagram of the current detection system in a 1st embodiment. It is a figure which shows the electrode structure in a semiconductor integrated circuit chip. It is sectional drawing of a semiconductor integrated circuit chip. FIG. 3 is a circuit diagram of a current read circuit in the first embodiment. It is a conceptual diagram of the electrode structure in the case of confirming the effect of a current detection apparatus by simulation. It is a figure which shows the simulation result of the density | concentration distribution of the reaction material at the time of an electric current detection. It is a figure which shows the simulation result of the time change of electrode current. In simulation, it is a figure which shows the relationship between an electrode size and a current gain. In simulation, it is a figure which shows the relationship between an electrode size and a current gain. It is sectional drawing of an electrode structure, and the conceptual diagram of a redox cycle. FIG. 6 is a circuit diagram of a current readout circuit in a second embodiment. It is a circuit diagram of a current buffer circuit. It is a figure of the amplifier using an operational amplifier, a switch, and a capacitor. It is a figure without occupying the modification of an electrode structure. It is a conceptual diagram when there is a level | step difference between a working electrode and an auxiliary electrode.

[First Embodiment]
Embodiments to which the present invention is applied will be described below with reference to the drawings. The embodiment of the present invention is not limited to the following embodiment, and can take various forms as long as they belong to the technical scope of the present invention.

  FIG. 1 is a block diagram showing a schematic configuration of a current detection system 1 to which the present invention is applied. As shown in FIG. 1, the current detection system 1 includes a solution cell 10, a reference electrode 20, a counter electrode 30, an operational amplifier 40, a voltage source 50, a personal computer 60, and a current detection device 70.

  The solution cell 10 is made of acrylic and serves as a solution tank into which the reference electrode 20 and the counter electrode 30 can be inserted. Here, the measurement electrolyte 12 dissolves the supporting electrolyte and the substance to be measured that causes an oxidation-reduction reaction.

The reference electrode 20 is used in a state immersed in the measurement solution in the solution cell 10 and is an electrode serving as a reference for the potential when the current of the measurement solution is measured, and is made of silver / silver chloride as a material.
The counter electrode 30 is used in a state of being immersed in the measurement solution in the solution cell 10, similarly to the reference electrode 20, and the circulation path of the current flowing from the working electrodes W _{11 to} W ₃₃ of the current detection device 70 described later. The electrode is made of platinum.

  The operational amplifier 40 has a non-inverting input terminal 42, an inverting input terminal 44, and an output terminal 46. The non-inverting input terminal 42 is connected to the output of the voltage source 50, and the inverting input terminal 44 has a reference electrode. 20 is connected. The counter electrode 30 is connected to the output terminal 46.

  With this configuration, the operational amplifier 40 has the potential of the reference electrode 20 equal to the potential applied from the voltage source 50 to the non-inverting input terminal 42 due to the virtual short circuit, and is held at that value. The electric current from the working electrode can be passed through.

The voltage source 50 is a constant voltage source that can adjust the value of the output voltage, is connected to the reference electrode 20, and applies a constant voltage to the reference electrode 20.
The personal computer 60 includes an A / D converter and a display screen (not shown), and the output side of the current detection device 70 is connected to the A / D converter. Then, the output of the current detection device 70 is converted into a digital signal by the A / D converter, and the converted result is displayed on the screen.

The current detection device 70 is a device that detects a current from a measurement solution that is a measurement target, and includes a semiconductor integrated circuit chip 72 and a micro control unit 74.
Here, details of the semiconductor integrated circuit chip 72 will be described with reference to FIGS. FIG. 2 is a diagram showing an electrode structure in the semiconductor integrated circuit chip 72, and FIG. 3 is a cross-sectional view of the semiconductor integrated circuit chip 72.

As shown in FIG. 2, the semiconductor integrated circuit chip 72 is provided with a plurality of current detection cells (S _{11 to} S ₃₃ ) in a matrix on a semiconductor substrate.
As shown in FIG. 2, each of the current detection cells (S _{11 to} S ₃₃ ) includes working electrodes W _{11 to} W ₃₃ formed in a substantially square shape and auxiliary electrodes a ₁₁ to W ₁₁ surrounding the working electrodes W _{11 to} W _33. It has a _33.

Each electrode of the semiconductor integrated circuit chip 72 is formed by exposing the uppermost metal wiring layer 76 of the CMOS chip to the chip surface as shown in FIG.
The electrodes and the readout circuit described later are produced by a 1.2 μm standard CMOS process. A 6-inch wafer is produced and diced for each chip. Thereafter, titanium and gold are deposited on the aluminum wiring layer exposed on the chip surface to form electrodes.

  Titanium is deposited on aluminum in order to adhere gold. Then, an electrode pattern is formed by etching. Further, a protective film 78 is formed and patterned so that the aluminum wiring layer is not exposed at the stepped portion.

The following (1) to (6) show the procedure for forming electrodes (working electrodes W _{11 to} W ₃₃ and auxiliary electrodes a _{11 to} a ₃₃ ).
(1) Chip cleaning First, cleaning with acetone, isopropyl alcohol (IPA), or ultrapure water (resistivity> 18.2 MOhm) is performed to remove stains due to organic substances and oils and fats adhering to the chip surface. . The chip is ultrasonically cleaned with acetone for 1 minute.

In order to remove acetone adhering to the chip surface, ultrasonic cleaning is performed using IPA for 1 minute. In order to remove IPA adhering to the chip surface, ultrasonic cleaning is performed for 1 minute using ultrapure water. After washing, the chip is baked at 120 ° C. for 30 minutes to remove moisture.
(2) Vapor deposition of metal for expansion gate Titanium (Ti) 20 nm and gold (Au) 50 nm are vapor-deposited on the chip as electrodes. The apparatus used was a resistance heating vacuum deposition apparatus. The degree of vacuum during vapor deposition is 5 × 10 ⁻³ Pa or less. The deposition rate is adjusted to be about 2 A / sec. Since the deposited Ti generates titanium oxide when it is exposed to air, it is necessary to deposit Au so as not to touch the air after the Ti is deposited.
(3) Optical photolithography A resist (OFPR-800LB) is spin-coated on the surface of the chip on which Au / Ti is laminated by a spin coater. The resist is spin-coated at 500 rpm for 5 seconds and at 4500 rpm for 30 seconds.

  Thereafter, pre-baking is performed at 90 ° C. for 1 minute using a hot plate. Subsequently, exposure is performed for 7 seconds with ultraviolet rays using a mask alignment apparatus, the mask pattern is transferred to a chip, and development is performed with a developer (NMD-3).

  OFPR-800LB is a positive resist, and the chemical structure of the resist at the location irradiated with ultraviolet rays changes and dissolves in an alkaline solution. The development is performed by immersing in a developer for 50 seconds, and immediately immersing in a new developer prepared in another beaker for 10 seconds.

The development is performed twice in order to prevent the resist dissolved in the developer from remaining on the chip surface by the first development.
Then, after rinsing twice for 60 seconds with ultrapure water, post-baking is performed at 120 ° C. for 30 minutes.

The electrode pattern is, the working electrode W ₁₁ to _W-33 is 25 [mu] m square square distance between the auxiliary electrode a ₁₁ ~a ₃₃ is 5 [mu] m, the width of the auxiliary electrode a ₁₁ ~a ₃₃ is 25 [mu] m. Further, the working electrode W ₁₁ to _W-33 are arranged in 170μm period.
(4) Au / Ti etching In order to form an electrode according to the mask pattern using the resist produced in (3), a portion of the metal not covered with the resist is etched. In order to perform etching of Au, immersion is performed at 30 ° C. for 2 minutes using AURUM-301.

Thereafter, rinsing with ultrapure water for 30 seconds is performed twice, and excess water is blown off by nitrogen blowing. Subsequently, using WLC-T adjusted to pH 8.0 by adding aqueous ammonia, Ti is etched by immersion at 30 ° C. for 2 minutes. Thereafter, similarly to the etching of Au, rinsing with ultrapure water for 30 seconds is performed again with nitrogen blowing.
(5) Removal of resist Finally, the resist is removed. The procedure is to immerse the chip in acetone for 1 hour or more to dissolve the resist. At this time, since the formed electrode may be peeled off, the ultrasonic cleaning is avoided unlike the operation (1).

Subsequently, it is cleaned by immersing it in IPA and ultrapure water for 1 minute without using ultrasonic cleaning. After nitrogen blowing, the excess water is evaporated by baking at 120 ° C. for 30 minutes.
(6) Formation of Protective Film 78 A resist (SU-8 3005) used as the protective film 78 is spin-coated on the surface of the chip on which the Au / Ti electrode is patterned by a spin coater. The resist is spin-coated at 500 rpm for 5 seconds and at 5500 rpm for 30 seconds.

  Thereafter, pre-baking is performed at 95 ° C. for 3 minutes using a hot plate. Subsequently, exposure is carried out with ultraviolet rays for 20 seconds using a mask alignment apparatus, the mask pattern is transferred to the chip, and development is performed with a developer (SU-8 Developer).

  SU-8 3005 is a negative resist, which forms a cross-linked structure at a position irradiated with ultraviolet rays and cures. The development is performed by immersing in a developer for 5 minutes and then immersing in a new developer prepared in another beaker for 10 seconds.

The development is performed twice in order to prevent the resist dissolved in the developer from remaining on the chip surface by the first development.
Then, after rinsing with IPA for 10 seconds, post-baking is performed at 200 ° C. for 2 minutes.

FIG. 2 shows a cross-sectional view of a chip on which the working electrodes W _{11 to} W ₃₃ , the auxiliary electrodes a _{11 to} a ₃₃ , and the protective film 78 are patterned.
The chip on which the electrode pattern and the protective film 78 are formed is held in a package, and wire bonding to the pads is performed. Further, in order to prevent the wiring portion from being immersed in the solution, a frame of silicon resin is placed immediately above the chip, and the outside is filled with the silicon resin.

As shown in FIG. 3, the uppermost metal wiring layer 76 is exposed in the shapes of the working electrodes W _{11 to} W ₃₃ and the auxiliary electrodes a _{11 to} a ₃₃ by the procedures (1) to (6).
Further, the solution cell 10 is placed on the semiconductor integrated circuit chip 72 sealed with silicon resin (see FIG. 1).

(Description of circuit configuration)
Next, the configuration of a circuit for reading the detected current from the working electrodes W _{11 to} W ₃₃ will be described with reference to FIG. FIG. 4 is a circuit diagram of the current readout circuit.

Readout circuit includes an amplifier 80, the holding circuit, the first switch Sa ₁₁ -SA ₃₃ and the second switch Sb ₁₁ ~Sb _33.
The amplifier 80 is an amplifier that detects current from the working electrodes W _{11 to} W ₃₃ , and includes an operational amplifier 82 and a resistor 84 as shown in FIG. The holding circuit is a circuit that holds the working electrodes W _{11 to} W ₃₃ at a predetermined potential, and is a wiring for supplying a predetermined voltage input from a voltage source (not shown) connected to the power supply terminal 86. .

Here, the voltage applied to the power supply terminal 86 is a voltage having a value in a range where the oxidation-reduction reaction of the measurement target substance occurs.
The first switches Sa _{11 to} Sa ₃₃ are switches provided between the inverting input terminal 81 of the operational amplifier 82 of the amplifier 80 and the working electrodes W _{11 to} W ₃₃ of the plurality of current detection cells S _{11 to} S ₃₃ . Then, it is opened (off) / closed (on) by an open / close command signal from the micro control unit 74.

The first switches Sa _{11 to} Sa ₃₃ are provided as semiconductor switches in the current detection cells S _{11 to} S ₃₃ .
The second switches Sb _{11 to} Sb ₃₃ are switches provided between the potential holding circuit and the working electrodes W _{11 to} W ₃₃ of the plurality of current detection cells S _{11 to} S ₃₃ . Open (off) / close (on) by open / close command signal.

Second switch Sb ₁₁ to SB _33, like the first switch Sa ₁₁ -SA _33, are provided as a semiconductor switch in the current sensing cell S ₁₁ to S _33.
(Operation of micro control unit 74)
The micro control unit 74 has a CPU, a ROM, a RAM, and an I / O (not shown). By the program stored in the ROM, all the first first switches Sa _{11 to} Sa ₁₁ are started at the start of the following (a) measurement. together to turn _33, and turn on all of the second switch Sb ₁₁ to SB _33, it is applied all at once voltage to the working electrode W ₁₁ to _W-33, to obtain a steady-state current.

(B) Turn on Sa ₁₁ among the first switch Sa ₁₁ ~Sa _33, and outputs a command signal for turning off the first switch Sa ₁₁ other Sa ₁₂ -SA ₃₃ was turned on.
(C) among the second switch Sb ₁₁ to SB _33, and the second switch Sb ₁₁ connected to the working electrode W _11, which is connected to the first switch Sa ₁₁ which is turned on and off, otherwise the A command signal for turning on the two switches Sb _{12 to} Sb ₃₃ is output.

(D) The switching operation of (a) and (c) is sequentially executed for all the first switches Sa _{11 to} Sa ₃₃ and the second switches Sb _{11 to} Sb ₃₃ .
(Operation during measurement)
At the time of current detection (during measurement), the voltage applied to the power supply terminal 86 is held in a range in which the oxidation-reduction reaction of the measurement target substance occurs, thereby forming a 3 × 3 array on the semiconductor integrated circuit chip 72. The potential of the arranged working electrodes W _{11 to} W ₃₃ is kept within the range where the redox reaction of the substance to be measured occurs, and a steady current is kept flowing through all the working electrodes W _{11 to} W ₃₃ , and the currents are read in order and measured. To do.

At this time, the potentials of the auxiliary electrodes a _{11 to} a ₃₃ are kept at a potential at which a reaction opposite to the oxidation-reduction reaction occurring at the working electrodes W _{11 to} W ₃₃ occurs.
By operating the current detecting device 70 as shown in the operation of the micro control unit 74, at the start of the measurement, all at the same time the voltage to the working electrode W ₁₁ to _W-33 is applied, since the steady-state current is obtained The current of each electrode is read out.

For example, when reading the working electrode W ₁₁ , the first switch Sa ₁₁ and the second switches Sb _{12 to} Sb ₃₃ are closed, the first switches Sa _{12 to} Sa ₃₃ and the second switch Sb ₁₁ are opened, while continued to flow constant current holding the potential of the working electrode W ₁₁ to _W-33 reads the current of the working electrode W _11.

When reading the working electrode W ₃₃ , the first switch Sa ₃₃ and the second switches Sb ₁₁ to Sb 32 are closed, the first switches Sa _{11 to} Sa ₃₂ and the second switch Sb ₃₃ are opened, and all the working electrodes W are opened. ₁₁ holding the potential of to _W-33, reads the current of the working electrode W ₃₃ while continuing to flow the constant current.

This also, by keeping the ON state one of the switches always either, holding the potential of all of the working electrode W ₁₁ to _W-33, the first switch Sa while flowing constant current ₁₁ -SA ₃₃ and The second switches Sb _{11 to} Sb ₃₃ are switched to read a specific cell.

(Confirmation of effect by simulation)
The effect of the electrode structure shown in FIG. 2 was confirmed by simulation. Using the finite element method analysis software COMSOL Multiphysics, numerical calculation was performed by solving a time-dependent diffusion equation in a space composed of an electrode and a solution. A conceptual diagram of the structure used for the calculation is shown in FIG.

FIG. 6 shows the calculation result of the concentration distribution of the reactant when the current is detected. 6A shows the calculation result of the conventional microelectrode array without the auxiliary electrodes a _{11 to} a ₃₃ , and FIG. 6B shows the calculation result of the microelectrode array shown in FIG.

The scale bar on the right side of FIG. 6 shows the concentration of the reactant in mM. Comparing the state of the diffusion layer, in the conventional microelectrode array of FIG. 6 (a), adjacent electrode diffusion layers overlap to form a planar diffusion, but in the microelectrode array of FIG. 6 (b), it can be seen that the diffusion layer is confined to the vicinity of the electrode by the auxiliary electrode a ₁₁ ~a _33.

The calculation results of the current amount of time variation of the working electrode W ₁₁ to _W-33 shown in FIG. In FIG. 7, when the solid line is a single microelectrode, the broken line indicates the calculation result of the conventional microelectrode array and the alternate long and short dash line indicates the calculation result of the microelectrode array shown in FIG.

  When comparing the amount of current, the steady current is not observed in the conventional microelectrode array and the amount of current decreases. However, in the electrode structure shown in FIG. 2, the steady current can be obtained even with the same electrode density. Furthermore, the amount of current is amplified as compared with a single microelectrode, and the time until a steady current is obtained is shortened to about 1/10.

Further, the amplification factor with respect to the amount of current in a single microelectrode was calculated, and the relationship with the electrode size was obtained in FIG. The amplification factor is the ratio of the value of the steady current in the proposed electrode structure to the steady current when the microelectrode is used alone. In the microelectrode, since the amount of current depends on the length rather than the area of the electrode, the characteristics are determined by the ratio of the lengths. L _WE: L _gap: if the ratio of L _AE same amplification factor was confirmed to be a substantially identical.

Further, in FIG. 9, as the increase amplification factor ratio of L _gap is small relative to L _WE, the amplification factor was confirmed to be saturated at L _AE / L _WE is 1.0 or more.
(Characteristics of current detection system 1)
In the current detection system 1 described above, as shown in FIG. 4, two switches (first switch and second switch) are used for one working electrode W _{11 to} W ₃₃ . The first switches Sa _{11 to} Sa ₃₃ are connected to the readout circuit, and the second switches Sb _{11 to} Sb ₃₃ are held at the potentials of the working electrodes W _{11 to} W ₃₃ inputted from the outside.

  Further, the non-inverting input terminal 83 of the operational amplifier of the readout circuit is also held at the same potential. As a result, an electrode that does not read out current can also hold the potential and continue to pass current.

  In the conventional microelectrode array, when the current is measured simultaneously, no steady current is observed and the amount of current decreases. However, in the microelectrode array structure of the current detection system 1 (see FIG. 2), the microelectrodes are the same. Steady current can be obtained even if accumulated at a density.

This is because, in the existing microelectrode array, the diffusion layers of adjacent electrodes overlap to form a planar diffusion layer (see FIG. 2), resulting in linear diffusion. On the other hand, in the microelectrode array structure of the current detection system 1, assisted by the electrodes a ₁₁ ~a ₃₃ is suppressed expansion of the diffusion layer, and a spherical diffusion layer is formed, the diffusion layer in the vicinity of microelectrodes (see FIG. 2) By being confined, local measurement can be performed as compared with the conventional electrode structure. Therefore, the electrodes are integrated more densely than the conventional electrode structure. Further, the switching circuit (the first switches Sa _{11 to} Sa ₃₃ and the second switches Sb _{11 to} Sb ₃₃ ) of the current detection system 1 allows a steady current to be generated in all the electrodes. The switch can be switched with the current flowing, and the current flowing through the specific cell can be read out. As a result, it is possible to perform current detection type electrochemical measurement at multiple points at high speed.

Further, an electrochemical measurement circuit is configured without using an operational amplifier that consumes a large amount of power and occupies a large area in the current detection cells S _{11 to} S ₃₃ . For this reason, it becomes possible to perform an electrochemical measurement with the current detection cells S _{11 to} S ₃₃ that are integrated with low power consumption and high density.

Further, the auxiliary electrode a ₁₁ ~a ₃₃ is held at a predetermined potential as the opposite redox reaction occurs between the working electrode W ₁₁ to _W-33. Therefore, as shown in FIG. 10, a redox cycle occurs between the working electrodes W _{11 to} W ₃₃ and the auxiliary electrodes a _{11 to} a ₃₃ .

  By this redox cycle, the amount of current is amplified as compared with the case where the same microelectrode is used alone. Further, since the time until the shape of the diffusion layer is stabilized is shortened, the time until the steady current is obtained is reduced to about 1/10.

Further, the current detector 70, the width of the auxiliary electrode a ₁₁ ~a ₃₃ is 1/2 or more of the width of the working electrode W ₁₁ to _W-33. Therefore, it is possible to sufficiently handle the product produced at the working electrode W ₁₁ to _W-33 in the auxiliary electrode a ₁₁ ~a _33, diffusion layer remains in the vicinity of the working electrode W ₁₁ to _W-33, overlapping the diffusion layer of each electrode Absent. Therefore, the quantitative determination of the reactant can be made more accurate.

Moreover, the spacing of the auxiliary electrodes a ₁₁ ~a ₃₃ and the working electrode W ₁₁ to _W-33 is smaller than the diffusion length of the analyte. Accordingly, since the redox cycle occurs efficiently, the current of the working electrode W ₁₁ to _W-33 is amplified. Therefore, since it is not influenced by noise, the quantification of the reactant can be made more accurate.

Further, there is no electrode between the working electrodes W _{11 to} W ₃₃ and the auxiliary electrodes a _{11 to} a ₃₃ having a height equal to or longer than the diffusion distance of the measurement target substance from the electrode surface. Therefore, it is possible to sufficiently handle the product formed at the working electrode W ₁₁ to _W-33 with auxiliary electrodes (a ₁₁ ~a _33), the diffusion layer remains in the vicinity of the working electrode W ₁₁ to _W-33, the diffusion layers of each electrode Do not overlap. Therefore, the quantitative determination of the reactant can be made more accurate.

[Second Embodiment]
Next, the switching circuit of the current detection device 70 according to the first embodiment (the current detection device 100 in which the current buffers circuit b _{11 to} b ₃₃ are combined with the first switches Sa _{11 to} Sa ₃₃ and the second switches Sb _{11 to} Sb ₃₃ is used. The second embodiment used will be described with reference to FIG.

  In addition, in 2nd Embodiment, since it is the same as that of the structure of the electric current detection system 1 in 1st Embodiment except the electric current detection apparatus 100, the same code | symbol is attached | subjected to the same component and the description is abbreviate | omitted.

In the current detection device 100 in the second embodiment, as shown in FIG. 11, the working electrodes W _{11 to} W ₃₃ and the switching circuit (the first switches Sa _{11 to} Sa ₃₃ and the second switch) of the current detection device 70 in the first embodiment are used. Current buffer circuits b _{11 to} b ₃₃ are inserted between the switches Sb _{11 to} Sb ₃₃ ).

In other words, the working electrode W ₁₁ to _W-33, via a current buffer circuit b ₁₁ ~b ₃₃ shown in FIG. 11, and is connected to the switching circuit.
The current buffer circuits b _{11 to} b ₃₃ duplicate the current flowing through the electrodes and use the duplicated current for reading, thereby reducing the influence on the measurement system. As shown in FIG. 12A, the current buffer circuits b _{11 to} b ₃₃ include the current buffer circuits b _{11 to} b ₃₃ shown in FIG. 12B and the OTA 120 (Operational Transducer Amplifier) shown in FIG. It is composed of a combination of

The current buffer circuits b _{11 to} b ₃₃ shown in FIG. 12B have two structures: a current mirror circuit that replicates the current and a source follower circuit that holds the potential of the electrode. These are connected symmetrically so that currents in both directions can flow.

When current flows out from the input terminals 130 of the current buffer circuits b _{11 to} b _33, the upper circuit operates and no current flows in the lower circuit. Further, when a current flows into the input terminals 130 of the current buffer circuits b _{11 to} b ₃₃ , the lower circuit operates and no current flows through the upper circuit. As for the circuit characteristics, the electrode potential is held at the ground potential, and the input current and the output current match.

In the current buffer circuits b _{11 to} b ₃₃ shown in FIG. 12B, there are two stable states, a state where the current buffer circuits b _{11 to} b ₃₃ operate normally and a high impedance state where no current flows.
In order to prevent the current buffer circuits b _{11 to} b _{33 from} entering a high impedance state, an OTA 120 shown in FIG. 12C is used as a startup circuit as shown in FIG.

The OTA 120 is a circuit that converts a difference between input voltages into a current. By connecting the OTA 120 as shown in FIG. 12A, when the electrode potential deviates from the ground potential, the circuit is changed to the operating state by forcing current to flow into the current buffer circuits b _{11 to} b ₃₃ . be able to. Once the current buffer circuits b _{11 to} b ₃₃ are in the operating state, the current buffer circuits b _{11 to} b ₃₃ hold the electrode potential at the ground potential, current flows, and the OTA 120 stops operating.

For example, w ₁₁ , b ₁₁ , Sa ₁₁ , Sb ₁₁ are set as one current detection cell S ₁₁ , and the cells are arranged in an array as shown in FIG. The auxiliary electrodes a _{11 to} a ₃₃ are connected by wiring so that potentials can be applied to all the auxiliary electrodes a _{11 to} a ₃₃ with one wiring.

In this circuit, since no operational amplifier is used for each of the current detection cells S _{11 to} S ₃₃ , the power consumption and the occupied area are small and suitable for integration.
(Effect of providing a current buffer circuit)
Connecting directly without using the working electrode W ₁₁ to _W-33 and the first switch Sa ₁₁ -SA ₃₃ and the second switch Sb ₁₁ to SB ₃₃ and the current buffer circuit b ₁₁ ~b _33, depending on the circumstances at the time of measurement, Although the potential of the electrode at the time instead of the first switch Sa ₁₁ -SA ₃₃ and the second switch Sb ₁₁ to SB ₃₃ is can vary, depending on the use of current buffer circuits b ₁₁ ~b _33, change in the potential due to switching of the switch Can be prevented from being transmitted to the electrode.

Therefore, the current of the measurement object can be measured more accurately under any circumstances.
Current buffer circuit b ₁₁ ~b ₃₃ is provided with a source follower circuit for holding current of the working electrode W ₁₁ acts as a current mirror circuit for duplicating the current to _W-33 electrode W ₁₁ to _W-33 to a predetermined potential, the Therefore, since the current buffer circuits b _{11 to} b ₃₃ can be realized without using an operational amplifier having a large power consumption and a large occupied area in the current detection cells S _{11 to} S ₃₃ , the power consumption is reduced and the occupied area is reduced. Can be small.

(Other embodiments)
Embodiments of the present invention are not limited to the above-described embodiments, and can take various forms as long as they belong to the technical scope of the present invention.

  (A) In the current read circuit, as shown in FIG. 13, in the amplifier 80 shown in FIGS. 4 and 11, the current may be converted into a voltage using the switch 112 and the capacitor 114 instead of using the resistor 84.

(B) The CMOS circuit is desirably created by a standard CMOS process, but may be arbitrarily selected according to the application. The technology may be arbitrarily selected according to the application.
The working electrodes W _{11 to} W ₃₃ and auxiliary electrodes a _{11 to} a ₃₃ (hereinafter also simply referred to as electrodes) are produced by exposing the uppermost metal wiring layer 76 of the CMOS chip to the chip surface. Another metal may be placed on the metal in order to prevent the metal wiring layer 76 in contact with the solution from being dissolved and to give the electrode functionality. Although it is assumed that the electrodes are formed on a chip, separately prepared electrodes may be connected to the integrated circuit.

  (C) If the material of each electrode has electroconductivity, a kind will not be restrict | limited especially, What is necessary is just to select arbitrarily according to a use. Examples include an electrically conductive material and a semiconductor material that falls between a metal and an insulator.

  Specific examples of the electrically conductive material include metals such as copper, nickel, aluminum, titanium, palladium, chromium, and stainless steel; noble metals such as gold, silver, and platinum; not limited to metals, graphite, glassy carbon, Examples include carbonaceous materials such as pyrolytic graphite, conductive carbon paste, and conductive diamond; and conductive polymer materials.

As the semiconductor material, p-type and n-type Si, Ge, diamond, GaAs, GaN, InP, GaP , CdS, ZnO, TiO 2, SiC, ITO, In 2 O 3, SnO 2, CdO, Cd 2 SnO 4 Etc. Any one of these materials may be used alone, or two or more of these materials may be used in any combination.

(D) The insulator and the material of the substrate between the working electrodes W11 to W33 and the auxiliary electrodes a11 to a33 are not particularly limited, and may be arbitrarily selected according to the application.
Examples include inorganic solid insulating materials (mica, asbestos, asbestos paper, electrical insulating cement board), insulating porcelains (feldspar porcelain, alumina porcelain, beryllia porcelain, steatite porcelain, forsterite porcelain, wollastonite porcelain, magnesia Porcelain, Elite porcelain, zircon porcelain), boron nitride, silicon nitride, dielectric porcelain (titanium porcelain, barium titanate porcelain), glass (quartz glass, high silicate glass, soda lime glass, lead glass, borosilicate glass, aluminosilicate Glass, silicate glass), glass ceramics (dehydroceramics), glass fibers (glass cloth, glass tape, storage battery glass mat), enamel, basalt, sulfur (Portland cement), fiber materials, wood, paper power cables Insulation, thermoplastic resin material, polyethylene (PE , Polyethylene copolymer, flame retardant polyethylene, polypropylene (PP), vinyl chloride resin, polyvinyl chloride (PVC) polystyrene (PS), AS resin, ABS resin, methacrylic resin, polycarbonate (PC), polyamide resin, polyester Resin, fluororesin, polytetrafluoroethylene (PTFE), fluorinated ethylene / propylene copolymer (Teflon (registered trademark) FEP), ethylene / tetrafluoroethylene copolymer (ETFE), polychlorinated trifluoroethylene , Polyvinylidene fluoride, polyethylene terephthalate (PET), polyimide resin, acrylic resin, acrylic resin, methacrylic resin, polyacrylonitrile resin, acetal resin, thermal effect resin (network polymer), epoxy resin, unsaturated polyester Resin, silicone resin, Nord resin, urea resin, melanin resin, alkyd resin, natural fiber material, rubber material, natural rubber, styrene butadiene rubber (SBR), butyl rubber, polybutene, ethylene propylene rubber, chloroprene rubber, chlorosulfonated polyethylene rubber, silicone rubber Fluorinated rubber, nitrile rubber, urethane rubber, thermoplastic rubber, crosslinked polyethylene (chemically crosslinked polyethylene, radiation crosslinked polyethylene, silane crosslinked polyethylene) and the like.

(D) The shape of the working electrodes W _{11 to} W ₃₃ is not limited to the square shown in FIG. 2, but may be any shape such as a rectangle or a circle without departing from the spirit of the present invention. It is. Further, each electrode may have a different shape.

(E) an auxiliary electrode a ₁₁ ~a ₃₃ also may take any shape without departing from the spirit of the present invention. Each electrode may have a different shape. It is also possible to connect all of the auxiliary electrode a ₁₁ ~a ₃₃ at the surface as shown in FIG. 14.

(F) The size of the working electrodes W _{11 to} W ₃₃ is preferably equal to or less than the diffusion distance (several tens μm square) of the measurement target substance. In general, an electrode called a microelectrode has a characteristic length of several tens of μm or less, and when it is larger than that, it does not exhibit characteristics as a microelectrode.

(G) distance between the working electrode W ₁₁ to _W-33 and the auxiliary electrode a ₁₁ ~a ₃₃ is sufficiently shorter than the diffusion length of the analyte (a few μm or less) is desirable. Increase the efficiency of the redox cycle, to enhance the amplification effect of the current, the distance between the working electrode W ₁₁ to _W-33 auxiliary electrode a ₁₁ ~a ₃₃ is preferably as small. However, if the interval is too small, securing sufficient electrical insulation and handling in a mass production process tends to be difficult.

(H) width of the auxiliary electrode a ₁₁ ~a ₃₃ is sufficient half the length of one side of the square of the working electrode W ₁₁ to _W-33. Generally as the width of the auxiliary electrode a ₁₁ ~a ₃₃ is large, the processing capacity of the products produced at the working electrode W ₁₁ to _W-33 is increased. If the width of the auxiliary electrode a ₁₁ ~a ₃₃ is smaller than half the length of one side of the working electrode W ₁₁ to _W-33, since fall ability to return the product generated at the working electrode W ₁₁ to _W-33 to the reaction The expansion of the diffusion layer cannot be suppressed.

The processing capacity of the auxiliary electrode a ₁₁ ~a ₃₃ width working electrode W ₁₁ be larger than half of the length of one side of the to _W-33 product does not change.
(I) between the working electrode W ₁₁ to _W-33 and the auxiliary electrode a ₁₁ ~a ₃₃ is better is flat. When there is a step 116 between the working electrodes W _{11 to} W ₃₃ and the auxiliary electrodes a _{11 to} a ₃₃ a ₁₁ as shown in FIG. 15, the step 116 is preferably smaller. If the wall is present between the working electrode W ₁₁ to _W-33 and the auxiliary electrode a ₁₁ ~a _33, it amplifies the effect of the current as the wall increases is reduced.

  This is because the step 116 reduces the redox cycle efficiency. Even if there is a step that is sufficiently shorter (approximately several μm) than the diffusion distance of the substance to be measured, the effect of suppressing the spread of the diffusion layer does not greatly decrease, so the time until a steady current is obtained. It won't be long.

(J) The number of electrodes is not particularly limited. One or more may be sufficient. However, in the present invention, it is assumed that a plurality of electrodes are used.
(K) Arrangement in the case of using a plurality of electrodes is also arbitrary. The electrodes are preferably provided in an integrated manner. The form of integration is not particularly limited, but examples include a so-called array type in which a plurality of rows and columns are arranged, and a capillary array type in which a large number of electrodes are arranged in a row.

In the electrode array shown in FIG. 2, nine electrodes are formed in an array of 3 columns × 3 rows.
(L) the electrode of the present invention is configured so as to apply a voltage to each of the working electrode W ₁₁ to _W-33. In the present invention, the voltage is applied using the current buffer circuits b _{11 to} b ₃₃ and the switching circuit, but the method of applying the voltage is not particularly limited.

(M) The method of forming the electrode pattern is not particularly limited. As a method for producing a plurality of working electrodes W _{11 to} W ₃₃ by insulating them with micro gaps of micron or sub-micron order, a combination of photolithography and dry etching method, lift-off method or ion milling method is combined. There is a method of manufacturing on a substrate.

The auxiliary electrode a ₁₁ ~a ₃₃ surrounding the (n) each working electrode W ₁₁ to _W-33, it is desirable to apply the same potential. Therefore, the auxiliary electrode a ₁₁ ~a ₃₃ together may be electrically connected to. Further, the wiring to the storage electrodes a ₁₁ ~a ₃₃ may be provided to allow application of a separate potential.

(O) does not necessarily need to be able to measure the current flowing to the auxiliary electrode a ₁₁ ~a _33. Optionally may be the measurement of the current through the auxiliary electrode a ₁₁ ~a _33.
(P) The materials of the reference electrode 20 and the counter electrode 30 are not particularly limited, and may be arbitrarily selected depending on the application. Further, such created on a CMOS chip, it may be created on the same substrate as the working electrode W ₁₁ to _W-33. A potentiostat may be used to realize the operation of the three-electrode system.

(Q) The solvent used for the measurement is not particularly limited, and may be water or a non-aqueous solvent. A solid electrolyte may be used.
(R) The reference electrode 20 and the counter electrode 30 may be configured by connecting the reference electrode 20 to the inverting input terminal 44 of the operational amplifier 40 and the counter electrode 30 to the output terminal. The operational amplifier 40 may be one on an integrated circuit chip. Further, since the current flowing through the reference electrode 20 becomes small, the operational amplifier 40 to be used preferably has an input current of the order of pA or less.

By using the switching circuit of the present invention and the current buffer circuits b _{11 to} b ₃₃ , it becomes possible to perform a current detection type electrochemical measurement at multiple points at high speed.
In the conventional microelectrode array, the steady current is not observed and the amount of current decreases. However, in the proposed electrode structure, the steady current can be obtained even if the microelectrodes are integrated at the same density. The amount of current is amplified as compared with a microelectrode of the same size used alone, and the time until a steady current is obtained is reduced to about 1/10.

  Furthermore, since the diffusion layer is confined in the vicinity of the microelectrode, local measurement can be performed as compared with the conventional electrode structure, so that a larger number of electrodes can be integrated in a limited space. In addition, the microelectrode array structure of the present invention can be realized without significant changes in the process of the microelectrode array used for conventional current detection.

  Therefore, in various fields that perform current detection type electrochemical measurement, for example, measurement of physiologically active substances in body fluids, clinical examination, manufacturing process management of foods, etc. Application is possible.

DESCRIPTION OF SYMBOLS 1 ... Current detection system, 10 ... Solution cell, 12 ... Measuring solution, 20 ... Reference electrode, 30 ... Counter electrode, 40 ... Operational amplifier, 42 ... Non-inverting input terminal, 44 ... Inverting input terminal, 46 ... Output terminal, 50 ... Voltage source 60 ... Personal computer 70 ... Current detection device 72 ... Semiconductor integrated circuit chip 74 ... Micro control unit 76 ... Metal wiring layer 78 ... Protective film 80 ... Amplifier 81 ... Inverting input terminal 82 ... op, 83 ... non-inverting input terminal, 84 ... resistors, 86 ... power supply terminal, 100 ... current detection unit, 112 ... switch, 114 ... capacitor, 116 ... stepped, 120 ... OTA, 130 ... input terminal, S ₁₁ to S ₃₃ ... current detection cell, Sa ₁₁ ~Sa ₃₃ ... first switch, Sb ₁₁ ~Sb ₃₃ ... second switch, W ₁₁ to _W-33 ... working electrode, a ₁₁ ~a ₃₃ ... auxiliary electrode , B ₁₁ ~b ₃₃ ... current buffer circuit.

Claims (7)

A plurality of current detection cells provided on a semiconductor substrate, surrounding the working electrode and the periphery of the working electrode, and having an auxiliary electrode held at a potential at which a redox reaction opposite to the working electrode occurs;
Current detecting means connected to the working electrode , detecting a current output from the working electrode, and controlling the working electrode to have a predetermined potential ;
A potential holding means connected to the working electrode and holding the working electrode at the predetermined potential;
A first switch connected between the current detection means and each working electrode of the plurality of current detection cells;
A second switch connected between the potential holding means and each working electrode of the plurality of current detection cells;
One of the first switches is turned on, and the other switches other than the turned on first switch are turned off, and the second switch is connected to the turned on first switch. Control means for sequentially performing a switching operation for turning off the second switch connected to the working electrode and turning on the other second switches for all the first switches and the second switches;
A current detection device comprising: The current detection device according to claim 1,
The current detection means includes
An amplifier having an inverting terminal and a non-inverting input terminal;
The inverting terminal is connected to the working electrode via the first switch;
The non-inversion terminal is connected to the working electrode through the second switch. In the current detection device according to claim 1 or 2,
An input terminal connected to the working electrode, and an output terminal connected to the first switch and the second switch, while holding the output current of the working electrode input to the input terminal, A current detection device comprising a current buffer circuit in the current detection cell for holding the potential of the working electrode at a predetermined potential. The current detection device according to claim 3,
The current buffer circuit includes:
A current mirror circuit that replicates the current of the working electrode; a source follower circuit that maintains the current of the working electrode at a predetermined potential;
A current detection device comprising: In the electric current detection apparatus of any one of Claims 1-4,
The width of the auxiliary electrode is ½ or more of the width of the working electrode. In the electric current detection apparatus of any one of Claims 1-5,
The current detection apparatus is characterized in that a distance between the working electrode and the auxiliary electrode is smaller than a diffusion distance of the substance to be measured. In the electric current detection apparatus of any one of Claims 1-6,
There is no current detection device between the working electrode and the auxiliary electrode having a height greater than the diffusion distance of the substance to be measured from the electrode surface.